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Molecular mechanism in regulation of the intramembrane proteases

Research Project

Project/Area Number 23657082
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionTohoku University

Principal Investigator

FUTAI Eugene  東北大学, (連合)農学研究科(研究院), 准教授 (90447459)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords酵素 / プロテアーゼ / 脳・神経 / 認知症 / 酵母
Research Abstract

Since intramenbrane proteases possess these active sites buried in the lipid bilayer, it is difficult to purify and measure their activities. We introduced human gamma-secretase complex in yeast and succeeded in measuring its activity in vitro with the yeast microsomes. In this research, we utilized the reconstition system and analyzed the enzymatic character of the gamma-secretase. We found the relationship between proteolytic activities and subunit composition, and we screened the modulator of the protease activities from lipids and natural compounds. Malfunction of gamma-secretase leads to Alzheimer's disease. We would like to expand our research to the treatment of the disease.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (19 results)

All 2013 2012 2011

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (11 results) Book (1 results)

  • [Journal Article] CTF1-51, a truncated carboxyl-terminal fragment of amyloid precursor protein, suppresses the effects of A β -lowering γ-secretase modulators2012

    • Author(s)
      Watahiki, H., Yagishita, S., Futai, E. & Ishiura, S
    • Journal Title

      Neurosci. Lett

      Volume: 526 Pages: 96-99

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Localization of mature neprylysin in lipid rafts2012

    • Author(s)
      Sato, K., Tanabe, C., Yoneyama, Y., Watahiki, H., Zhao, Y., Yagishita, S., Ebina, M., Suo, S., Futai, E., Murata, M. & Ishiura, S
    • Journal Title

      J. Neurosci. Res

      Volume: 90 Pages: 870-877

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ -secretase complex2012

    • Author(s)
      Nagara, Y., Hagiyama, M., Hatano, N., Futai, E., Suo, S., Takaoka, Y., Murakami, Y., Ito, A. & Ishiura, S
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 417 Pages: 462-467

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Localization of mature neprilysin in lipid rafts.2012

    • Author(s)
      Sato K, Tanabe C, Yonemura Y, Watahiki H, Zhao Y, Yagishita S, Ebina M, Suo S, Futai E, Murata M, Ishiura S.
    • Journal Title

      J. Neurosci. Res.

      Volume: 90 Issue: 4 Pages: 870-877

    • DOI

      10.1002/jnr.22796

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CTF1-51, a truncated carboxyl-terminal fragment of amyloid precursor protein, suppresses the effects of Aβ42-lowering γ-secretase modulators.2012

    • Author(s)
      Watahiki H, Yagishita S, Futai E, Ishiura S.
    • Journal Title

      Neurosci. Lett.

      Volume: 526 Issue: 2 Pages: 96-99

    • DOI

      10.1016/j.neulet.2012.08.029

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of presenilin 1 and presenilin 2 γ-secretase activities using a yeast reconstitution system2011

    • Author(s)
      Yonemura, Y., Futai, E., Yagishita, S., Suo, S., Tomita, T., Iwatsubo, T. & Ishiura, S
    • Journal Title

      J. Biol. Chem

      Volume: 286 Pages: 44569-44575

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of presenilin 1 and presenilin 2 γ-secretase activities using a yeast reconstitution system.2011

    • Author(s)
      Yonemura, Y., Futai, E., Yagishita, S., Suo, S., Tomita, T., Iwatsubo, T. & Ishiura, S.
    • Journal Title

      J. Biol. Chem.

      Volume: 286 Pages: 44569-44575

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] プレセニリンとAph1 分子の違いがγセクレターゼの機能に及ぼす影響2013

    • Author(s)
      米村洋而, 二井勇人, 柳下聡介, 石浦章一
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-05
    • Related Report
      2013 Final Research Report
  • [Presentation] 酵母再構成系を用いたγセクレターゼの機能解析2013

    • Author(s)
      米村洋而, 二井勇人, 柳下聡介, 周防諭, 石浦章一
    • Organizer
      第17回病態プロテアーゼ学会学術集会
    • Place of Presentation
      浜松
    • Year and Date
      2013-08-10
    • Related Report
      2013 Final Research Report
  • [Presentation] プロリン異性化酵素Pin1 はPresenilin に結合し, 活性を制御する2013

    • Author(s)
      佐々木広美, 二井勇人, 内田隆史
    • Organizer
      2013年度日本農芸化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2013-03-25
    • Related Report
      2013 Final Research Report
  • [Presentation] 酵母再構成系を用いたγセクレターゼの機能解析2013

    • Author(s)
      米村洋而、二井勇人、柳下聡介、周防諭、石浦章一
    • Organizer
      第17回病態プロテアーゼ学会学術集会
    • Place of Presentation
      オークラアクトシティホテル浜松
    • Related Report
      2013 Annual Research Report
  • [Presentation] プレセニリンとAph1分子の違いがγセクレターゼの機能に及ぼす影響2013

    • Author(s)
      米村洋而、二井勇人、柳下聡介、石浦章一
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Annual Research Report
  • [Presentation] プロリン異性化酵素Pin1はPresenilin1に結合し、活性を制御する2013

    • Author(s)
      佐々木広美、二井勇人、内田隆史
    • Organizer
      2013年度日本農芸化学会大会
    • Place of Presentation
      仙台市
    • Related Report
      2012 Research-status Report
  • [Presentation] 酵母再構成系によるγセクレターゼ活性の評価2012

    • Author(s)
      米村洋而, 二井勇人, 柳下聡介, 周防諭, 石浦章一
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-14
    • Related Report
      2013 Final Research Report
  • [Presentation] エタノールアミン型リン脂質のγセクレターゼのin vitro 活性への影響2012

    • Author(s)
      小野寺智子, 佐々木広美, 二井勇人, 内田隆史, 神尾好是, 金子淳
    • Organizer
      2012年度日本農芸化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2012-03-25
    • Related Report
      2013 Final Research Report
  • [Presentation] 酵母再構成系によるγセクレターゼ活性の評価2012

    • Author(s)
      米村洋而、二井勇人、柳下聡介、周防諭、石浦章一
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Research-status Report
  • [Presentation] 酵母再構成系によるγセクレターゼにおけるPS1とPS2 の比較2011

    • Author(s)
      米村洋而, 二井勇人, 柳下聡介, 周防諭, 富田泰輔, 岩坪威, 石浦章一
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-15
    • Related Report
      2013 Final Research Report
  • [Presentation] γセクレターゼによるAβ生成へのPin1 の作用機構解析2011

    • Author(s)
      佐々木広美, 内田隆史, 二井勇人
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-14
    • Related Report
      2013 Final Research Report
  • [Book] 脳-分子・遺伝子・生理-2011

    • Author(s)
      石浦章一, 笹川昇, 二井勇人
    • Publisher
      裳華房
    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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